Investigation for molecular mechanisms underlying the establishment of "pre"-leukemic stem cells aiming for therapy and prevention of leukemia

• Project/Area Number: 22591054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: TSUZUKI Shinobu 愛知県がんセンター(研究所), 遺伝子医療研究部, 室長 (00342965)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 前白血病 / 白血病性幹細胞

Research Abstract

"Pre"-leukemic stage is crucial for the establishment of leukemia. Elucidation of mechanisms underlying the pre-leukemic stage would pave the way to the development of therapy and preventive measures of leukemia. We have successfully modeled "pre"-leukemic stage of TEL-AML1 leukemia in mice, and thus identified 4 genes essential for the establishment of "pre"-leukemic cells. The 4 genes are also essential for the maintenance of leukemia, providing the rationale for strategy of targeting the genes for therapy and prevention of leukemia.

Research Products

• [Journal Article] TEL(ETV6)-AML1(RUNX1) Initiates Self-renewing Fetal Pro-B Cells in Association with a Transcriptional Program Shared with Embryonic Stem Cells in Mice. (2013)
  • Author(s): Tsuzuki S and Seto M.
  • Journal Title: Stem Cells Volume: 31 Issue: 2 Pages: 236-247
  • DOI: 10.1002/stem.1277
  • Peer Reviewed
• [Journal Article] Expansion of functionally defined mouse hematopoietic stem and progenitor cells by a short isoform of RUNX1/AML1. (2012)
  • Author(s): Tsuzuki S and Seto M.
  • Journal Title: Blood Volume: 119(3) Issue: 3 Pages: 727-735
  • DOI: 10.1182/blood-2011-06-362277
  • Peer Reviewed
• [Journal Article] Promotion and maintenance of leukemia by ERG. (2011)
  • Author(s): Tsuzuki S, Taguchi O, Seto M.
  • Journal Title: Blood. Volume: 117(14) Issue: 14 Pages: 3858-3868
  • DOI: 10.1182/blood-2010-11-320515
  • Peer Reviewed
• [Journal Article] Promotion and maintenance of leukemia by ERG (2011)
  • Author(s): Tsuzuki S
  • Journal Title: Blood Volume: 117 Pages: 3858-3868
  • Peer Reviewed
• [Presentation] Cooperation of altered AML1/RUNX1 with BCR-ABL in inducing blast crisis-like disease of chronic myelogenous leukemia. (2012)
  • Author(s): 都築忍
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: ロイトン札幌(札幌)
  • Year and Date: 2012-09-19
• [Presentation] Altered differentiation and enhanced self-renewal activity of B cells by the leukemia-associated TEL(ETV6)-AML1(RUNX1) fusion gene (2011)
  • Author(s): Shinobu Tsuzuki
  • Organizer: 第70回2011 日本癌学会学術集会シンポジウム(International Symposium: Dysregulated differentiation program in cancer)
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-03
• [Presentation] Altered differentiation and enhanced self-renewal activity of B cells by the leukemia-associated TEL (ETV6)-AML1 (RUNX1) fusion gene (2011)
  • Author(s): 都築忍
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-03
• [Presentation] ERG発現による白血病化 (2010)
  • Author(s): 都築忍
  • Organizer: 第6回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-23
• [Presentation] ERG発現による白血病化 (2010)
  • Author(s): 都築忍
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-23
• [Presentation] Cooperation of altered AML1/RUNX1 with BCR-ABL in inducing blast crisis-like disease of chronic myelogenous leukemia.
  • Author(s): 都 築 忍
  • Organizer: 第７１回日本癌学会総会
  • Place of Presentation: ロイトン札幌（札幌）
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/